School of Cancer Sciences, University of Birmingham, Birmingham, UK.
Br J Haematol. 2012 Dec;159(5):589-98. doi: 10.1111/bjh.12072. Epub 2012 Oct 1.
NKG2D (KLRK1) is an activating receptor on natural killer (NK) and T-cells and binds a diverse panel of polymorphic ligands encoded by the MIC and RAET1 gene families. We studied the clinical importance of retinoic acid early transcript-1 (RAET1) polymorphism in allogeneic stem cell transplantation (SCT) by determining the frequency of 18 single nucleotide polymorphisms (SNPs) and individual RAET1 alleles in 371 patient-donor pairs and relating this to clinical outcome. A strong association was observed between the presence of five SNPs within the patient RAET1L (ULBP6) gene and relapse-free survival and overall survival. Two common alleles of RAET1L were determined and the presence of the protective RAET1L02 allele in the patient was associated with a relapse-free survival of 44% at 8 years compared with just 25% in patients who lacked a RAET1L02 allele (P < 0·001). Overall survival at this time was 55% in those with RAET1L02 allele compared to 39% in patients who lacked a RAET1L02 allele (P = 0·003). These novel findings indicate a critical role for NKG2D-RAET1L interactions in determining SCT clinical outcome and show RAET1L may have an important influence on regulating the strength of the alloreactive immune response. The data will be of value in guiding the development of future transplant therapy protocols.
NKG2D（KLRK1）是自然杀伤（NK）细胞和 T 细胞上的一种激活受体，可结合由 MIC 和 RAET1 基因家族编码的多种多态配体。我们通过确定 371 对患者-供体对中的 18 个单核苷酸多态性（SNP）和个体 RAET1 等位基因的频率，研究了同种异体干细胞移植（SCT）中视黄酸早期转录物-1（RAET1）多态性的临床重要性，并将其与临床结果相关联。在患者 RAET1L（ULBP6）基因内存在五个 SNP 与无复发生存和总生存之间存在很强的相关性。确定了两个常见的 RAET1L 等位基因，并且患者中保护性 RAET1L02 等位基因的存在与无 RAET1L02 等位基因患者的无复发生存率为 44%（8 年）相比，无 RAET1L02 等位基因患者的无复发生存率为 25%（P < 0·001）。此时，具有 RAET1L02 等位基因的患者的总生存率为 55%，而缺乏 RAET1L*02 等位基因的患者为 39%（P = 0·003）。这些新发现表明 NKG2D-RAET1L 相互作用在确定 SCT 临床结果方面起着关键作用，并表明 RAET1L 可能对调节同种异体反应性免疫反应的强度具有重要影响。这些数据将有助于指导未来移植治疗方案的制定。
